1-(2,4,6-Triisopropylphenyl)ethylamine
O]+, 374 (58) [M + H - H2O]+; IR 3577, 3052, 1724 cm-1. Anal.
Calcd for C24H41NO3: C, 73.61; H, 10.55; N, 3.58. Found: C,
73.93; H, 10.62; N, 3.52.
Anal. Calcd for C26H45NO3: C, 74.42; H, 10.81; N, 3.34. Found:
C, 74.31; H, 10.94; N, 3.29.
(2S*,4R*)-Methyl 4-(hydroxy-((S*)-1-(2,4,6-triisopropylphe-
nyl)ethyl)amino)-2,5-dimethylhexanoate (rac-11a) (for experi-
mental conditions, see Scheme 3): white crystals; mp 133-135
°C (MeOH); 1H NMR δ 0.96 (d, J ) 6.9 Hz, 3H), 1.04 (d, J ) 6.8
Hz, 3H), 1.18-1.30 (m, 24H), 1.66-1.84 (m, 2H), 2.31-2.47 (m,
1H), 2.72-2.98 (m, 3H), 3.31-3.48 (m, 1H), 3.69 (s, 3H), 4.02-
4.18 (m, 1H), 4.07-4.12 (m, 1H), 4.88 (q, J ) 6.9 Hz, 1H), 6.95
(s, 1H), 7.03 (s, 1H); 13C NMR δ 18.5, 18.7, 19.0, 22.0, 23.6, 23.7,
24.0, 24.1, 24.6, 25.3, 27.8, 29.2, 30.2, 33.7, 36.1, 51.0, 56.6, 62.0,
120.5, 122.8, 134.5, 146.3, 146.4, 148.1, 177.6; MS (DCI) m/z 420
(100) [M + H]+, 402 (34) [M + H - H2O]+; IR 3579, 3053, 1731,
1606, 1455 cm-1. Anal. Calcd for C26H45NO3: C, 74.42; H, 10.81;
N, 3.34. Found: C, 74.38; H, 10.90; N, 3.36.
(R)-Ethyl 4-(hydroxy-((R)-1-(2,4,6-triisopropylphenyl)ethyl)-
amino)hexanoate ((R,R)-9b): yellow oil; [R]20 -14.9 (c 1.5,
D
CHCl3); 1H NMR δ 0.99 (t, J ) 7.6 Hz, 3H), 1.20-1.29 (m, 21H),
1.32 (d, J ) 6.9 Hz, 3H), 1.34-1.55 (m, 1H), 1.81-1.95 (m, 3H),
2.48 (t, J ) 7.4 Hz, 2H), 2.78-2.87 (m, 2H), 3.41 (sept, J ) 7.2
Hz, 1H), 4.00 (s, 1H), 3.98-4.05 (m, 1H), 4.13 (q, J ) 7.2 Hz,
2H), 4.78 (q, J ) 6.9 Hz, 1H), 6.95 (s, 1H), 7.02 (s, 1H); 13C NMR
δ 11.6, 14.3, 18.6, 19.4, 23.6, 23.9, 23.9, 24.6, 24.9, 25.3, 25.6,
28.3, 29.4, 31.2, 33.9, 56.7, 60.1, 61.3, 120.7, 123.0, 134.7, 146.5,
146.6, 148.3, 174.5; MS (DCI) m/z 406 (44) [M + H]+, 388 (100)
[M + H - H2O]+; IR 3580, 3056, 1725 cm-1. Anal. Calcd for
C25H43NO3: C, 74.03; H, 10.69; N, 3.45. Found: C, 73.95; H,
10.65; N, 3.46.
(2R*,4R*)-Methyl 4-(hydroxy ((S*)-1-(2,4,6-triisopropylphe-
nyl)ethyl)amino)-2,5-dimethylhexanoate (rac-11b) (for experi-
mental conditions, see Scheme 3): white solid; mp 78-80 °C; 1H
NMR δ 0.96 (d, J ) 7.1 Hz, 3H), 1.07 (d, J ) 6.8 Hz, 3H), 1.18
(d, J ) 6.9 Hz, 6H), 1.24 (d, J ) 7.0 Hz, 12H), 1.29 (d, J ) 6.7
Hz, 3H), 1.34 (d, J ) 7.0 Hz, 3H), 2.14-2.27 (m, 1H), 2.38-2.49
(m, 1H), 2.77-2.91 (m, 3H), 3.31-3.48 (m, 1H), 3.69 (s, 3H),
3.90 (br s, 1H), 3.95-4.04 (m, 1H), 4.90 (q, J ) 7.0 Hz, 1H), 6.96
(s, 1H), 7.02 (s, 1H); 13C NMR δ 15.4, 18.9, 19.3, 22.3, 23.7, 23.8,
23.9, 24.3, 24.9, 25.3, 28.3, 29.2, 29.4, 33.9, 35.4, 51.5, 56.7, 61.2,
120.7, 122.9, 134.7, 146.5, 146.6, 148.2, 178.2; MS (DCI) m/z 420
(22) [M + H]+, 419 (100) [M + NH4 - H2O]+; IR 3492, 3050,
(R)-Ethyl 4-(hydroxy-((S)-1-(2,4,6-triisopropylphenyl)ethyl)-
amino)-6-methylheptanoate ((S,R)-9c): white solid; mp 55-56
°C; [R]20D +25.7 (c 1.4, CHCl3); 1H NMR δ 0.95 (d, J ) 6.4 Hz,
3H), 0.99 (d, J ) 6.4 Hz, 3H), 1.19-1.34 (m, 24H), 1.43-1.57
(m, 2H), 1.60-1.77 (m, 1H), 1.78-2.03 (m, 2H), 2.38-2.60 (m,
2H), 2.85 (sept, J ) 6.9 Hz, 1H), 2.99-3.09 (m, 1H), 3.43 (sept,
J ) 6.8 Hz, 1H), 3.91 (br s, 1H), 4.06 (sept, J ) 6.8 Hz, 1H), 4.14
(q, J ) 7.0 Hz, 2H), 4.77 (q, J ) 7.0 Hz, 1H), 6.96 (d, J ) 1.9 Hz,
1H), 7.02 (d, J ) 1.9 Hz, 1H); 13C NMR δ 14.3, 19.2, 21.7, 23.7,
23.9, 23.9, 24.3, 24.5, 24.9, 25.4, 25.4, 26.5, 28.2, 29.4, 31.0, 33.9,
34.2, 56.3, 57.4, 60.1, 120.7, 123.0, 134.8, 146.5, 146.6, 148.3,
174.5; MS (DCI) m/z 434 (100) [M + H]+; IR 3494, 3030, 1731,
1600, 1461 cm-1. Anal. Calcd for C27H47NO3: C, 74.78; H, 10.92;
N, 3.23. Found: C, 74.47; H, 10.73; N, 3.08.
(R)-Ethyl 4-(hydroxy-((S)-1-(2,4,6-triisopropylphenyl)ethyl)-
amino)-5-methylhexanoate ((S,R)-9d): colorless oil; [R]20D +12.1
(c 1.4, CHCl3); 1H NMR δ 0.99 (d, J ) 6.8 Hz, 3H), 1.06 (d, J )
6.8 Hz, 3H), 1.21-1.32 (m, 24H), 1.74-1.80 (m, 1H), 1.94-2.03
(m, 1H), 2.32-2.42 (m, 1H), 2.47 (dd, J ) 7.2, 6.7 Hz, 2H), 2.74
(dt, J ) 10.2, 2.9 Hz, 1H), 2.85 (sept, J ) 6.9 Hz, 1H), 3.35-3.48
(m, 1H), 3.92 (br s, 1H), 3.93-4.07 (m, 1H), 4.13 (q, J ) 7.1 Hz,
2H), 4.87 (q, J ) 6.9 Hz, 1H), 6.96 (s, 1H), 7.02 (s, 1H); 13C NMR
δ 14.3, 19.1, 19.6, 20.9, 22.2, 23.7, 23.8, 23.9, 24.5, 25.0, 25.1,
25.4, 28.1, 29.4, 31.5, 33.8, 56.9, 60.0, 63.7, 120.7, 123.0, 134.6,
146.4, 146.6, 148.3, 174.5; MS (DCI) m/z 420 (49) [M + H]+,
402 (100) [M + H - H2O]+; IR 3489, 3030, 1731, 1609, 1466
cm-1. Anal. Calcd for C26H45NO3: C, 74.42; H, 10.81; N, 3.34.
Found: C, 74.08; H, 10.73; N, 3.19.
1739, 1608, 1550, 1456 cm-1
.
(S*,E)-Ethyl 4-(hydroxy((S*)-1-(2,4,6-triisopropylphenyl)-
ethyl)amino)-5-methylhex-2-enoate (rac-12) (for experimental
conditions, see Scheme 3): white crystals; mp 127-129 °C
1
(MeOH); H NMR δ 0.69 (d, J ) 6.8 Hz, 3H), 0.94 (d, J ) 6.9
Hz, 3H), 0.97 (d, J ) 6.8 Hz, 3H), 1.11 (d, J ) 6.8 Hz, 6H), 1.17
(d, J ) 6.9 Hz, 9H), 1.22 (t, J ) 7.1 Hz, 3H), 1.42 (d, J ) 6.5 Hz,
3H), 1.82-1.95 (m, 1H), 2.66 (t, J ) 9.0 Hz, 1H), 2.77 (sept, J )
6.9 Hz, 1H), 3.10-3.22 (m, 1H), 3.88-4.02 (m, 1H), 4.12 (q, J )
7.1 Hz, 2H), 4.39 (q, J ) 6.5 Hz, 1H), 4.57 (br s, 1H), 5.34 (d, J
) 16.1 Hz, 1H), 6.84 (s, 1H), 6.91 (s, 1H), 7.21 (dd, J ) 16.1, 9.3
Hz, 1H); 13C NMR δ 14.2, 20.0, 20.1, 21.6, 22.4, 23.8, 23.9, 25.0,
25.8, 26.0, 28.3, 29.5, 30.3, 33.8, 59.8, 60.1, 70.1, 121.0, 122.7,
124.8, 132.8, 146.0, 146.2, 147.1, 148.4, 165.9; MS (DCI) m/z 418
(23) [M + H]+, 400 (100) [M + H - H2O]+; IR 3579, 3479, 3054,
1710, 1645, 1606, 1568, 1467 cm-1. Anal. Calcd for C26H43NO3:
C, 74.77; H, 10.38; N, 3.35. Found: C, 74.76; H, 10.62; N, 3.16.
General Procedure for the Preparation of γ-N-Acetoxyamino
Esters 14a-e. A stirred solution of 0.5 mmol of the γ-N-
hydroxyamino ester 9 in 10 mL of dry CH2Cl2 under argon was
treated with 0.052 mL (56 mg, 0.55 mmol) of freshly distilled acetic
anhydride. The solution was stirred at 40 °C until completion (TLC),
and then concentrated under vacuum. The residue was filtered
through a plug of silica gel with 10% ethyl acetate in pentane to
afford the acetylated product (13a-e, 92-98% yield).
This material was stirred at 20 °C with 2.0 mL of a 5% solution
of TFA in dichloromethane until complete transformation of the
starting material (TLC), and then a saturated aqueous solution of
NaHCO3 was added. The mixture was extracted with dichlo-
romethane, which was washed with brine, dried over MgSO4,
filtered, and concentrated under vacuum. Purification of the residue
by chromatography on silica gel with 5-50% ethyl acetate in
pentane afforded the γ-N-acetoxyamino ester (14a-e, 66-83%
yield).
(S)-Ethyl 4-cyclohexyl-4-(hydroxy((R)-1-(2,4,6-triisopropyl-
phenyl)ethyl)amino)butanoate ((R,S)-9e): colorless oil; [R]20
D
-8.5 (c 1.2, CHCl3); 1H NMR δ 1.03-1.42 (m, 28H), 1.56-1.83
(m, 6H), 1.94-2.09 (m, 3H), 2.45 (t, J ) 6.9 Hz, 2H), 2.63-2.68
(m, 1H), 2.85 (sept, J ) 6.9 Hz, 1H), 3.35-3.48 (m, 1H), 3.91 (br
s, 1H), 3.98-4.11 (m, 1H), 4.14 (q, J ) 7.1 Hz, 2H), 4.88 (q, J )
6.9 Hz, 1H), 6.96 (s, 1H), 7.02 (s, 1H); 13C NMR δ 14.1, 19.5,
22.0, 23.5, 23.7, 23.8, 24.3, 25.0, 25.2, 26.4, 26.6, 27.1, 28.0, 29.4,
29.8, 31.6, 32.1, 33.7, 36.1, 56.8, 59.9, 64.1, 120.6, 122.8, 134.5,
146.2, 146.5, 148.1, 174.3; MS (DCI) m/z 460 (100) [M + H]+,
442 (64) [M + H - H2O]+; IR 3567, 3056, 1731, 1608, 1466 cm-1
;
HRMS(ESI) calcd for C29H50NO3 460.3785, found 460.3786.
(3S*,4S*)-Methyl 4-(hydroxy-((S*)-1-(2,4,6-triisopropylphe-
nyl)ethyl)amino)-3,5-dimethylhexanoate (rac-10) (for experimen-
tal conditions, see Scheme 3): white crystals; mp 133-135 °C
1
(MeOH); H NMR δ 0.94 (d, J ) 6.8 Hz, 3H), 1.07 (d, J ) 6.7
Hz, 3H), 1.15-1.31 (m, 21H), 1.36 (d, J ) 6.8 Hz, 3H), 2.22-
2.45 (m, 3H), 2.62-2.70 (m, 2H), 2.82-2.87 (m, 1H), 3.42-3.47
(m, 1H), 3.64 (s, 3H), 3.67-3.76 (m, 1H), 4.07-4.12 (m, 1H),
4.97 (q, J ) 6.8 Hz, 1H), 6.96 (s, 1H), 7.02 (s, 1H); 13C NMR δ
17.6, 19.9, 21.1, 23.0, 23.4, 23.6, 23.7, 24.6, 24.9, 25.2, 26.0, 27.9,
29.2, 30.3, 33.6, 40.1, 51.1, 57.9, 67.0, 120.6, 122.6, 134.4, 146.4,
147.8, 173.8, 190.4; MS (DCI) m/z 420 (18) [M + H]+, 402 (100)
(R)-Ethyl 4-(ethanoyloxyamino)pentanoate ((R)-14a): colorless
oil; [R]20D +11.2 (c 1.4, CHCl3); 1H NMR δ 1.04 (d, J ) 6.4 Hz,
3H), 1.19 (t, J ) 7.1 Hz, 3H), 1.56-1.63 (m, 2H), 2.03 (s, 3H),
2.35 (ddd, J ) 6.9, 6.8, 3.7 Hz, 2H), 3.05 (sext, J ) 6.4 Hz, 1H),
4.07 (q, J ) 7.2 Hz, 2H); 13C NMR δ 14.1, 17.6, 19.1, 28.9, 30.5,
55.6, 60.4, 170.9, 173.3; MS (DCI) m/z 204 (69) [M + H]+; IR
[M + H - H2O]+; IR 3501, 3030, 1745, 1610, 1573, 1460 cm-1
.
3244, 1736 cm-1
.
J. Org. Chem, Vol. 72, No. 2, 2007 491